Cancer of the urinary bladder affects 4 to 5 times more men than women worldwide. Cigarette smoking, occupational exposures and infection with Schistosoma haematobium are well-established risk factors for this malignancy. Furthermore, several genetic polymorphisms have been associated with increased bladder cancer risk. Important gaps in knowledge remain about synergistic effects between environmental factors, gene-environment interactions, and gender differences in bladder cancer risk factors. Egypt represents a unique setting for such research, as bladder cancer continues to be the most common malignancy in men in Egypt despite recent reductions in schistosomiasis, and the ratio of men to women remains consistently high; few women in Egypt smoke cigarettes (< 5%) compared to 50-70% of men; and in addition to the transitional cell type carcinoma that is predominantly observed world wide, squamous type carcinoma is very common in Egypt. We therefore propose to conduct a case-control study of bladder cancer in Egypt, with a sample size of 3,312 cases and 4 population-based controls per case. The Specific Aims of the study are as follows: 1) to evaluate environmental risk factors for bladder cancer, in men and women combined, including infections, and interactions among these factors; 2) to determine if associations between risk factors and bladder cancer are affected by gender; 3) to evaluate associations between bladder cancer risk (in men and women combined) and functional polymorphism in genes that mediate the oxidative stress response; 4) to evaluate interactions between environmental exposures and the candidate susceptibility genes, and to determine if gene-environment interactions exert differential effects on bladder cancer risk in men and women. Within these aims we will account for risk differences by histological type of bladder cancer (transitional vs. squamous). The results of this study will help establish the best preventive measures for bladder cancer in men and women, by appropriately directing the resources of the public health sector for effective cancer control. [unreadable] [unreadable]